EVIDENCE FOR CPP32 ACTIVATION IN THE ABSENCE OF APOPTOSIS DURING T-LYMPHOCYTE STIMULATION

Cysteine proteases of the interleukin-1 beta-converting enzyme family have been implicated in the effector process of apoptosis in several s ystems. Among these, CPP32 has been shown to be processed to active en zyme at the onset of apoptosis. Here, we show that CPP32 precursor is cleaved into its active form during phytohaemaglutinin A activation of T lymphocytes. Maximal processing is observed between day 3 and day 4 following addition of mitogen and is a transient process. Precursor c leavage is associated with the appearance of a CPP32-like enzymatic ac tivity in cell lysates. At this time in the culture, almost no apoptot ic cell and no dead cell can be detected, and T lymphocytes are active ly proliferating. CPP32 processing also occurs when lymphocytes are st imulated through an allogeneic primary mixed lymphocyte reaction, Our results suggest that proteolytic activation of CPP32 could be a physio logical step during T lymphocyte activation. In addition, these data i ndicate that CPP32 activation can occur independently of programmed ce ll death in T lymphocytes.